Significance

It was proposed that individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit delays in brain maturation. In the last decade, resting state functional imaging has enabled detailed investigation of neural connectivity patterns and has revealed that the human brain is functionally organized into large-scale connectivity networks. In this study, we demonstrate that the developing relationships between default mode network (DMN) and task positive networks (TPNs) exhibit significant and specific maturational lag in ADHD. Previous research has found that individuals with ADHD exhibit abnormalities in DMN–TPN relationships. Our results provide strong initial evidence that these alterations arise from delays in typical maturational patterns. Our results invite further investigation into the neurobiological mechanisms in ADHD that produce delays in development of large-scale networks.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood, and there is great interest in understanding its neurobiological basis. A prominent neurodevelopmental hypothesis proposes that ADHD involves a lag in brain maturation. Previous work has found support for this hypothesis, but examinations have been limited to structural features of the brain (e.g., gray matter volume or cortical thickness). More recently, a growing body of work demonstrates that the brain is functionally organized into a number of large-scale networks, and the connections within and between these networks exhibit characteristic patterns of maturation. In this study, we investigated whether individuals with ADHD (age 7.2–21.8 y) exhibit a lag in maturation of the brain’s developing functional architecture. Using connectomic methods applied to a large, multisite dataset of resting state scans, we quantified the effect of maturation and the effect of ADHD at more than 400,000 connections throughout the cortex. We found significant and specific maturational lag in connections within default mode network (DMN) and in DMN interconnections with two task positive networks (TPNs): frontoparietal network and ventral attention network. In particular, lag was observed within the midline core of the DMN, as well as in DMN connections with right lateralized prefrontal regions (in frontoparietal network) and anterior insula (in ventral attention network). Current models of the pathophysiology of attention dysfunction in ADHD emphasize altered DMN–TPN interactions. Our finding of maturational lag specifically in connections within and between these networks suggests a developmental etiology for the deficits proposed in these models.